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Targeted therapies for non-small cell lung cancer

As researchers have learned more about the changes in lung cancer cells that help them grow, they have developed newer drugs that specifically target these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs. They sometimes work when chemo drugs don’t, and they often have different (and less severe) side effects. At this time, they are most often used for advanced lung cancers, either along with chemo or by themselves.

Drugs that target tumor blood vessel growth (angiogenesis)

For tumors to grow, they must form new blood vessels to keep them nourished. This process is called angiogenesis. Some targeted drugs, called angiogenesis inhibitors, block this new blood vessel growth.

Bevacizumab (Avastin®) is an angiogenesis inhibitor used to treat advanced non-small cell lung cancer. It is a monoclonal antibody (a man-made version of a specific immune system protein) that targets vascular endothelial growth factor (VEGF), a protein that helps new blood vessels to form.

This drug is often used with chemo for a time. Then if the cancer responds, the chemo may be stopped and the bevacizumab is given by itself until the cancer starts growing again.

Ramucirumab (Cyramza®) is another angiogenesis inhibitor that can be used to treat advanced non-small cell lung cancer. VEGF has to bind to proteins called receptors to act. This drug is a monoclonal antibody that targets a certain type of receptor for VEGF. This helps stop the formation of new blood vessels.

This drug is most often given after another treatment stops working. It is often combined with chemo.

These drugs can have side effects that are different from (and may add to) those of chemotherapy. Some of these can be serious, and can include problems with bleeding as well as blood clots. Rarely, these drugs can cause a hole to form in the intestine or stomach (called a perforation). These drugs can also cause problems with wound healing and so need to be stopped prior to surgery.

Because of the risks of bleeding, these drugs aren’t used in patients who are coughing up blood or who are on drugs considered blood thinners. The risk of serious bleeding in the lungs is higher in patients with the squamous cell type of lung cancer, which is why most current guidelines do not recommend using bevacizumab in patients with this type of lung cancer.

Drugs that target EGFR

Epidermal growth factor receptor (EGFR) is a protein found on the surface of cells. It normally helps the cells to grow and divide. Some NSCLC cells have too much EGFR, which causes them to grow faster. Drugs that target EGFR used to treat non-small cell lung cancer (NSCLC) include:

Erlotinib and afatinib block the signal from EGFR that tells cells to grow. They can be used alone (without chemo) as the first treatment for advanced NSCLCs that have certain mutations in the EGFR gene. These are more common in women and people who haven’t smoked. Erlotinib is also used for advanced NSCLC without those mutations if chemo isn’t working. Both erlotinib and afatinib are pills.

Common side effects of these drugs include:

Skin problems

Diarrhea

Mouth sores

Loss of appetite

Skin problems can include an acne-like rash on the face and chest, which in some cases can lead to skin infections.

For more detailed information on the skin problems that can result from anti-EGFR drugs, see our document Targeted Therapy.

Drugs that target the ALK gene

About 5% of NSCLCs have been found to have a rearrangement in a gene called ALK. This change is most often seen in non-smokers (or light smokers) who have the adenocarcinoma subtype of NSCLC. The ALK gene rearrangement produces an abnormal ALK protein that causes the cells to grow and spread. Drugs that target ALK include:

These drugs block the abnormal ALK protein and can shrink tumors in patients whose lung cancers have the ALK gene change. Although they can help after chemo has stopped working, they are often used instead of chemo in people whose cancers have the ALK gene rearrangement.